During bacterial chemotaxis, cells such as Escherichia coli detect temporal changes in the concentration of specific chemicals and respond to these changes by modulation of the sense of rotation of the flagellar rotary motors. The response appears to consist of two phases, an "excitatory" phase which signals the flagella motors to rotate in the appropriate sense and an "adaptive" phase during which the flagellar signal is counteracted. The pathway for information flow is becoming clear. It appears that a series of phosphoryl transfer reactions are responsible for the excitatory phase and this pathway feeds back onto the adaptive pathway by modulating the activity of methylesterase enzyme, CheB, which regulates the methylation level of the receptor proteins which in turn controls the signalling properties of the receptor. This proposal is concerned with defining the chemical mechanism of information flow from the receptors to the flagella and to CheB. Muc of the focus of this proposal concerns CheB. This multifunction enzyme acts as an amidase, methylesterase and as a phosphatase, atcepting phosphate moieties from the excitatory pathway and hydrolysing those phosphates. In turn the methylesterase activity of CheB is likely to be regulated by its phosphorylation state. A series of genetic and biochemical approaches are outlined to define how CheB interacts with the excitatory pathway and to define how the methylation state and ligand occupancy state of the receptors interact to generate the excitatory signals.